A randomised controlled trial conducted in Switzerland explored whether open-label placebos — pills openly identified as containing no active ingredient — could help reduce premenstrual symptoms. The study included 150 women aged 18–45 with moderate-to-severe PMS, and notably, over half also met criteria for PMDD.
Participants were divided into three groups: one received placebo pills along with a detailed explanation of how placebos can still help (including information about placebo effects in PMS research), another received the same pills but with minimal explanation, and a third group continued their usual care. The placebo pills were taken twice daily for six weeks, spanning two menstrual cycles.
The group that received placebos with a thorough explanation experienced the largest improvements — a 79% reduction in symptom intensity and an 83% reduction in how much symptoms interfered with daily life. These improvements were significantly greater than in the other two groups. Interestingly, the group that received placebos without the explanation did not improve significantly more than those who received no placebo at all. This suggests that understanding how and why a treatment might work — even a placebo — plays an important role in the response.
The safety profile was encouraging: only four mild side effects were reported among the 100 women taking placebos, and adherence was very high at 93%. The researchers noted that the effect sizes seen with the explained placebo were comparable to, or even larger than, those typically reported for SSRIs used to treat PMS. While more research is needed before open-label placebos could become a standard recommendation, these findings highlight the powerful role that information, expectations, and transparent communication may play in managing premenstrual symptoms.
Key findings
- OLP with treatment rationale (OLP+) showed a large effect on symptom intensity reduction compared to treatment as usual at MC3 (d=0.90, p<0.001) and a medium effect compared to OLP without rationale (d=0.55, p=0.036)
- OLP+ reduced PMS interference compared to TAU (d=0.55, p=0.022) and compared to OLP without rationale (d=0.48, p=0.044) at MC3
- OLP without treatment rationale did not significantly differ from treatment as usual for either symptom intensity (d=0.35, p=0.177) or interference (d=0.06, p=0.799)
- The OLP+ group showed a 79.3% reduction in symptom intensity and 82.5% reduction in interference from baseline to MC3
- Only 4 non-serious adverse events were reported across both OLP groups (n=100), and adherence was high at 93.18%
- 96.7% of participants (145/150) completed the trial, and 52.7% of participants also met criteria for premenstrual dysphoric disorder
Methods, briefly
Three-arm randomised controlled trial (N=150) conducted in Switzerland from 2018–2020. Women aged 18–45 with moderate-to-severe PMS or PMDD were randomized 1:1:1 to OLP with treatment rationale (OLP+, n=50), OLP without rationale (OLP–, n=50), or treatment as usual (TAU, n=50). The intervention consisted of two placebo pills daily for 6 weeks across two menstrual cycles. PMS was assessed prospectively using a validated daily symptom diary across three menstrual cycles (one baseline, two intervention). Linear mixed-effects models were used for intention-to-treat analysis. Sensitivity analyses included completers-only and exclusion of days with stressful events/illness.
Limitations to keep in mind
- Self-report data may be subject to social desirability bias
- Trial was advertised as a study for a side-effect free intervention, potentially attracting participants more open to unconventional treatments, limiting generalisability
- No blinding was possible given the open-label nature of the intervention
- Participants were relatively young (mean age 25.3 years), predominantly single (92%), and many were students, which may limit external validity
- Patients and the public were not involved in trial design, conduct, or reporting
- After adjusting for multiple comparisons, some between-group differences became non-significant (e.g., interference at MC3 between OLP+ and TAU: adjusted p=0.195)
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